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Dissertation
Effects of GM1 administration on the neurochemistry, neuroanatomy and chronic behavior of MPTP-lesioned non-human primates with Parkinsonism
Doctor of Philosophy (Ph.D.), Allegheny University of the Health Sciences
Oct 1997
DOI:
https://doi.org/10.17918/00007488
Abstract
GM1 ganglioside has previously been shown to produce behavioral improvement in non-human primates, made parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrdine (MPTP). The first part of this dissertation sought to further characterize the neuroanatomical and neurochemical effect of GM1 treatment in non-human primates made rapidly parkinsonian with MPTP. The studies examined the number of residual TH-positive neurons and the expression of tyrosine hydroxylase (TH) mRNA per neuron in the ventral mesencephalon. The densities of dopamine D1 and D2 receptors were assessed to examine GM1 effects on postsynaptic receptors in the striatum. The density of GABAA receptors in the globus pallidus as well as enkephalin and substance P mRNA expression in the striatum were evaluated to determine GM1's effect on basal ganglia output pathways. The results of these studies showed, in comparison with saline-treated control animals, GM1 administration resulted in a greater number of residual DAergic neurons, increased TH mRNA expression in residual DAergic neurons, reduced levels of striatal DA D1 receptor binding and ENK mRNA expression, increased striatal Sub P mRNA expression, and increased GABAA receptor binding in the GPe. The second part of this dissertation examined the effects of GM1 treatment in a slowly progressing model of PD, as well as assessed the sequelae of parkinsonian symptoms. Chronic low dose MPTP was administered to non-human primates over a two+ year period. During the first 26 weeks the animals were given only MPTP and the sequelea of early cognitive and motor deficits was assessed using various behavioral tasks. GM1 treatment was than added to the MPTP administration for 90 weeks. The chronic treatment effects of GM1 as compared to the progression of deficits in an untreated group were followed. The results showed that early intervention with GM1 reverses early-appearing cognitive deficits, may protect against further cognitive decline and may slow the progression of parkinsonian motor symptoms as parkinsonism progresses. Together, with recent positive data from clinical trials of GM1 in PD this evidence suggests the usefulness of GM1 treatment in both the early and late stages of Parkinson's disease.
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Details
- Title
- Effects of GM1 administration on the neurochemistry, neuroanatomy and chronic behavior of MPTP-lesioned non-human primates with Parkinsonism
- Creators
- Anne Margaret Pope-Coleman
- Contributors
- Jay S. Schneider (Advisor) - Drexel University, Allegheny University of the Health Sciences (1996-1998)
- Awarding Institution
- Allegheny University of the Health Sciences
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Allegheny University of the Health Sciences; Philadelphia, Pennsylvania
- Number of pages
- xvi, 223 pages, 8 unnumbered pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Anatomy (and Neurobiology) [Historical]; Allegheny University of the Health Sciences (1996-1998); School of Medicine (1996-1998)
- Other Identifier
- 991021888779504721